Coagulopathy and blood component transfusion in trauma

1. Coagulopathy and blood component transfusion in trauma R3 정상우

2. Trauma • 1 in 10 death worldwide • uncontrolled bleeding • 40% of trauma-related deaths • leading cause of potentially preventable and early in-hospital death • life-threatening bleeding • vascular injury • coagulopathy • consumption and dilution of coagulation factors and platelets, dysfunction of platelets and the coagulation system, increased fibrinolysis, compromise of the coagulation system by the infusion of colloid, hypocalcemia, and disseminated intravascular coagulation-like syndrome

3. Pathophysiology of coagulopathy in trauma2) Consumption coagulopathy • precise cause is difficult to identify and multifactorial

4. Pathophysiology of coagulopathy in trauma3) Increased fibrinolysis • trauma pts. demonstrate both hypofibrinolytic and hyperfibrinolytic states • severity of injury, time from injury에 따라 달라진다 • Simmons et al. • trauma 직후 : fibrinolytic activity increase • mild~moderate inj.: 24h 이후 normal • major inj.: remain elevated • hypothermia : fibrinolytic activity 증가

5. Pathophysiology of coagulopathy in trauma4) Hypothermia-induced coagulopathy • significant risk factors for life-threatening coagulopathy • injury severity score > 25 • systolic BP < 70mmHg • acidosis with pH < 7.10 • hypothermia with BT < 34℃ • lethal triad • hypothermia, metabolic acidosis, progressive coagulopathy

6. Pathophysiology of coagulopathy in trauma4) Hypothermia-induced coagulopathy • effect of hypothermia on coagulopathy is difficult to identify by routine coagulation screening tests (PT, aPTT) • hypothermia • impairs thrombin generation and the formation of platelet plugs and fibrin clots • increase clot lysis • results in coagulopathy and uncontrollable bleeding

7. Pathophysiology of coagulopathy in trauma5) Decreased levels of coagulation factors and platelets • large volumes of crystalloid and colloid • thrombocytopenia is seen commonly in pts. received massive blood transfusion • platelets are present in whole blood • 현재는 RBC unit 사용 • negligible amounts of coagulation factors and platelets • thrombocytopenia and subnormal levels of coagulation factors often occur at early stage during massive RBC transfusion

8. Pathophysiology of coagulopathy in trauma6) The effect of acute RBC loss on coagulation • unclear • as no data from trauma pts. are available, the effect of acute RBC loss on coagulation is unknown

9. Effect of massive RBC transfusion on coagulation • 과거 수혈은 주로 whole blood에 의존, 현재는 specific component therapy • blood component therapy • optimizes the use of resources by allowing components to be used in different pts. • avoids potentially harmful effects caused by transfusion of surplus constituents • whole blood와 비교했을 때 massive RBC transfusion 시 earlier stage에서 coagulopathy 발생 (low levels of platelets and clotting factors)

10. Effect of massive RBC transfusion on coagulation • relationship between volume of blood loss, replacement volume and the reduction in coagulation factor and platelet levels are difficult to establish • increased acid load from RBC units may also contribute to coagulopathy • pH of an RBC unit is low, and decreases progressively during storage from 7.0 to 6.3 • plasma의 high-buffering capacity로 acid-base disturbance는 잘 일어나지 않는다 • trauma pts. are already acidotic, massive transfusion of RBCs further increase acid load, exacerbate the ongoing coagulopathy

11. Unresolved issues regarding blood transfusion in trauma1) Optimal replacement therapy for FFP and platelets • massive RBC transfusion 시 FFP, platelets, fibrinogen concentrate or cryoprecipitate를 같이 줘야한다는 건 알고 있지만 universal guideline은 없다 • based on experts’ opinion or personal experience

12. Unresolved issues regarding blood transfusion in trauma1) Optimal replacement therapy for FFP and platelets • 1st approach • transfuse FFP and plts. prophylactically after a certain number of units of RBCs • FFP:RBC → 1:10 ~ 2:3 • plt:RBC → 6:10 ~ 12:10 • coagulopathy의 발생을 예방하거나 bleeding을 줄인다는 증거는 없다 • benefit도 확실하지 않다

13. Unresolved issues regarding blood transfusion in trauma1) Optimal replacement therapy for FFP and platelets • 2nd approach • transfuse FFP, plt, cryoprecipate only when there is clinical or laboratory evidence of coagulopathy • microvascular bleeding • PT or aPTT > 1.5 times normal value • thrombocytopenia < 50000 • fibrinogen concentration < 1g/L • occult site의 microvascular bleeding은 발견하기 힘들다 • lab. test may take 30~60min

14. Effect of RBC transfusion on longer-term outcome in trauma1) Multiple organ failure (MOF) • RBC transfusion has been to shown to be an independent risk factor for post-injury MOF • 513명의 major trauma, severe bleeding and haemorrhagic shock 환자에 대한 연구에서 injury MOF 발생한 환자는 첫 12h 이내에 RBC 13unit 수혈받음 • MOF 발생하지 않은 환자는 3.8unit • decrease in volume of RBC transfused may decrease the risk and severity of MOF

15. Effect of RBC transfusion on longer-term outcome in trauma2) Post-injury infection • large amounts of foreign antigens may lead to downregulation of the immune system • alternative non-immune-mediated mechanism • stored RBCs are less deformable and more rigid, once transfused they may obstruct capillary blood flow, predisposing tissue to ischemia and infection as well as poor delivery of prophylactic antibiotics

16. The need for haemostatic agents • ideal hemostatic agent should be efficacious in a wide range of hemostatic dysfunctions, simple to store and use, and have a rapid action • activated recombinant factor Ⅶ (rFⅦa) is a potential candidate • effective hemostasis in a wide range of bleeding conditions • significantly dcreased RBC transfusion requirement in pts. with major trauma • optimal preconditions should be achieved before administration

17. The need for haemostatic agents • optimal preconditions • fibrinogen concentration ≥ 0.5g/L • platelet count ≥ 50/L • pH ≥ 7.2

18. Conclusions • non-surgically correctable bleeding remains a major challenge • currently, blood component replacement therapy remains the mainstay of coagulopathy-related bleeding • although RBC transfusion can be life-saving, its negative effects on post-injury outcome have been well documented • hemostatic agents, which can effectively control bleeding and reduce the amount of RBC required, may decrease mortality and morbidity in trauma pts. but are unlikely to replace blood transfusion completely